Screening for Transthyretin Amyloidosis During Carpal Tunnel Release: An Opportunity for Early Diagnosis

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive infiltrative disease of the myocardium. Early diagnosis is essential for the timely initiation of disease-modifying therapies. Carpal tunnel syndrome (CTS) often precedes cardiac manifestations by several years, making carpal tunnel release (CTR) a unique window for tissue-based screening. This review summarizes current evidence on the prevalence of transthyretin (TTR) deposits during CTR, explores clinical risk factors, and proposes a multidisciplinary management pathway for biopsy-positive patients. Reported prevalence of TTR deposits during CTR varies substantially across studies (9.3% to 34%), reflecting differences in patient demographics, surgical techniques, and biopsy protocols. Key predictors of biopsy positivity include advanced age, male sex, bilateral CTS, and a history of spinal stenosis or trigger finger. Overall, 19.4% of patients in aggregated cohorts had TTR-positive biopsies; however, only approximately 2.3% of all screened patients were found to have concomitant ATTR-CM, corresponding to 1 newly identified case for every 43 patients undergoing biopsy. We emphasize that a positive tenosynovial biopsy should be interpreted as evidence of extracardiac transthyretin amyloid deposition rather than established systemic disease. Accordingly, biopsy-positive patients should undergo a structured cardiac evaluation, including biomarkers, electrocardiography, echocardiography, and when appropriate, bone scintigraphy. Biopsy during CTR is a powerful case-finding tool. However, it should be integrated into a structured, long-term multidisciplinary surveillance program. Longitudinal studies are needed to determine the conversion rate from isolated extracardiac deposition to clinical heart failure and to refine the cost-effectiveness of universal versus targeted screening.